An investigation is proposed exploring the use of biochemical reagents to improve fatigue resistance of intervertebral disc tissue. While not well quantified, the capacity of spinal tissue to withstand repetitive loading is a critically important factor in the progression of spinal osteoarthritis. Current treatments for spinal instability and low-back pain, including spinal fusion, are generally ineffective in slowing the progression of degeneration. Biochemical alterations in the structure of the annular matrix could have significant effects on the disc's ability to withstand repetitive mechanical loading. We intend to study the effectiveness of certain reagents in maintaining the mechanical properties of disc tissues subjected to non-traumatic fatigue loading. Preliminary experiments in our laboratory using novel destructive and non-destructive mechanical testing techniques have shown degradation of elastic-plastic and viscoelastic material properties of disc tissues subjected to non-traumatic cyclic loads. If these reagents are effective in improving fatigue resistance of intervertebral discs, a new, minimally invasive treatment may be developed which will be able to improve the degenerated disc's ability to withstand repetitive physiological loads. This type of treatment has the potential of improving or even replacing numerous surgical interventions directed at the ubiquitous problems of low back pain and instability. PROPOSED COMMERCIAL APPLICATION: Back pain and disability associated with spinal degeneration and instability is without question one of the costliest health problems in western civilization (in the range of $20 billion U.S. annually- low-back-pain alone). The commercial potential of a minimally invasive treatment (perhaps a series of injections) capable of arresting degradation and stabilizing intervertebral discs would be staggering. In addition, such treatment could be used as an additional preventative procedure in fusion surgery, where accelerated degeneration commonly occurs at the level adjacent to the fusion.